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Olle R Lindberg, Andrew McKinney, Jane R Engler, Gayane Koshkakaryan, Henry Gong, Aaron E Robinson, Andrew J Ewald, Emmanuelle Huillard, C David James, Annette M Molinaro, Joseph T Shieh, Joanna J Phillips
Abnormal activation of the epidermal growth factor receptor (EGFR) due to a deletion of exons 2-7 of EGFR (EGFRvIII) is a common alteration in glioblastoma (GBM). While this alteration can drive gliomagenesis, tumors harboring EGFRvIII are heterogeneous. To investigate the role for EGFRvIII activation in tumor phenotype we used a neural progenitor cell-based murine model of GBM driven by EGFR signaling and generated tumor progenitor cells with high and low EGFRvIII activation, pEGFRHi and pEGFRLo. In vivo, ex vivo, and in vitro studies suggested a direct association between EGFRvIII activity and increased tumor cell proliferation, decreased tumor cell adhesion to the extracellular matrix, and altered progenitor cell phenotype...
October 12, 2016: Oncotarget
Fei-Yi-Fan Wang, Chun-Sheng Kang, Si-Yi Wang-Gou, Chun-Hai Huang, Cheng-Yuan Feng, Xue-Jun Li
Epidermal Growth Factor like domain 7 (EGFL7), also known as Vascular Endothelial-statin (VE-statin), is a secreted angiogenic factor. Recent data have demonstrated the potential oncogenic role and prognostic significance of EGFL7 in several human cancers. However, the clinical signature and further mechanisms of EGFL7's function in gliomagenesis are poorly understood. In the present study, we found that increased EGFL7 expression was associated with tumor grade. High expression of EGFL7 in EGFRvIII-positive glioblastoma multiforme (GBM) was determined to be a strong and independent risk factor for reduced life expectancy...
October 7, 2016: Cancer Letters
H-C Lu, J Ma, Z Zhuang, F Qiu, H-L Cheng, J-X Shi
OBJECTIVE: Glioma is the most lethal form of cancer that originates mostly from the brain and less frequently from the spine. Glioma is characterized by abnormal regulation of glial cell differentiation. The severity of the glioma was found to be relaxed in isocitrate dehydrogenase 1 (IDH1) mutant. The present study focused on histological discrimination and regulation of cancer stem cell between IDH1 mutant and in non-IDH1 mutant glioma tissue. PATIENTS AND METHODS: Histology, immunohistochemistry and Western blotting techniques are used to analyze the glioma nature and variation in glioma stem cells that differ between IDH1 mutant and in non-IDH1 mutant glioma tissue...
August 2016: European Review for Medical and Pharmacological Sciences
Paolo Bossi, Carlo Resteghini, Nicholas Paielli, Lisa Licitra, Silvana Pilotti, Federica Perrone
EGFR is an extensively studied biomarker in head and neck squamous cell carcinoma (HNSCC). In this review, we discuss the prognostic and predictive role of EGFR in HNSCC, focusing on the different molecular alterations in specific treatment modalities such as radiotherapy alone (RT), combination of surgery, RT and chemotherapy (CT), EGFR inhibitors. We considered EGFR at different molecular levels: protein expression, protein activation, gene copy number, polymorphisms, mutation, EGFRvIII expression and EGFR ligand expression...
August 19, 2016: Oncotarget
Sameer A Greenall, Terrance G Johns
No abstract text is available yet for this article.
2016: Cell Death Discovery
Ilaria Giusti, Marianna Di Francesco, Vincenza Dolo
Glioblastoma is the most common and most malignant form of primary brain cancer and it is characterized by one of the highest mortality among human cancers. Maximal and aggressive surgical resection is the first approach treatment but it is not usually definitive, being the tumor characterized by a high proliferative rate and an extensive invasion. An early diagnosis, associated to a careful monitoring, is pivotal in glioblastoma treatment; the Magnetic Resonance Imaging is used for monitoring purpose, but it's not sensitive enough to detect very small tumors; a valid alternative could be a repeated biopsy, but it is associated to a significant morbidity: less invasive options for diagnosis and therapeutic monitoring are unfailingly researched...
August 13, 2016: Current Cancer Drug Targets
Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Kamal Veisi, Asghar Tanomand, Bahman Akbari
Phage display is a prominent screening technique for development of novel high affinity antibodies against almost any antigen. However, removing false positive clones in screening process remains a challenge. The aim of this study was to develop an efficient and rapid method for isolation of high affinity scFvs by removing NSBs without losing rare specific clones. Therefore, a novel two rounds strategy called invert biopanning was developed for isolating high affinity scFvs against EGFRvIII antigen from human scFv library...
August 9, 2016: Biologicals: Journal of the International Association of Biological Standardization
Christopher D Graham, Niroop Kaza, Barbara J Klocke, G Yancey Gillespie, Lalita A Shevde, Steven L Carroll, Kevin A Roth
Glioblastomas (GBMs) are the most common and aggressive primary human malignant brain tumors. 4-Hydroxy tamoxifen (OHT) is an active metabolite of the tamoxifen (TMX) prodrug and a well-established estrogen receptor (ER) and estrogen-related receptor antagonist. A recent study from our laboratory demonstrated that OHT induced ER-independent malignant peripheral nerve sheath tumor (MPNST) cell death by autophagic degradation of the prosurvival protein Kirsten rat sarcoma viral oncogene homolog. Because both MPNST and GBM are glial in cell origin, we hypothesized that OHT could mediate similar effects in GBM...
August 11, 2016: Journal of Neuropathology and Experimental Neurology
Adan Rios, Sigmund H Hsu, Angel Blanco, Jamie Buryanek, Arthur L Day, Mary F McGuire, Robert E Brown
UNLABELLED: Glioblastoma multiforme (GBM) is a CNS (central nervous system) malignancy with a low cure rate. Median time to progression after standard treatment is 7 months and median overall survival is 15 months [1]. Post-treatment vasculogenesis promoted by recruitment of bone marrow derived cells (BMDCs, CD11b+ myelomonocytes) is one of main mechanisms of GBM resistance to initial chemoradiotherapy treatment [2]. Local secretion of SDF-1, cognate ligand of BMDCs CXCR4 receptors attracts BMDCs to the post-radiation tumor site...
2016: Oncoscience
Fausto J Rodriguez, M Adelita Vizcaino, Ming-Tseh Lin
Gliomas represent the most common primary intraparenchymal tumors of the central nervous system in adults and children and are a genetic and phenotypic heterogeneous group. Large multi-institutional studies and The Cancer Genome Atlas have provided firm insights into the basic genetic drivers in gliomas. The main molecular biomarkers routinely applied to evaluate diffuse gliomas include MGMT promoter methylation, EGFR alterations (eg, EGFRvIII), IDH1 or IDH2 mutations, and 1p19q co-deletion. Many of these markers have become standard of care for molecular testing and prerequisites for clinical trial enrollment...
September 2016: Journal of Molecular Diagnostics: JMD
Sonoko Atsumi, Chisato Nosaka, Hayamitsu Adachi, Tomoyuki Kimura, Yoshihiko Kobayashi, Hisashi Takada, Takumi Watanabe, Shun-Ichi Ohba, Hiroyuki Inoue, Manabu Kawada, Masakatsu Shibasaki, Masabumi Shibuya
BACKGROUND: EGFRvIII is a mutant form of the epidermal growth factor receptor gene (EGFR) that lacks exons 2-7. The resulting protein does not bind to ligands and is constitutively activated. The expression of EGFRvIII is likely confined to various types of cancer, particularly glioblastomas. Although an anti-EGFRvIII vaccine is of great interest, low-molecular-weight substances are needed to obtain better therapeutic efficacy. Thus, the purpose of this study is to identify low molecular weight substances that can suppress EGFRvIII-dependent transformation...
2016: BMC Cancer
Carter M Suryadevara, Rupen Desai, Samuel Harrison Farber, Patrick C Gedeon, Adam Swartz, David Snyder, James Herndon, Patrick Healy, Bryan D Choi, Peter Edward Fecci, Luis Sanchez-Perez, John H Sampson
INTRODUCTION: Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is an effective immunotherapy for hematological cancers but requires a rethinking for clinical efficacy against solid tumors, where CARs have largely failed. Lymphodepletive preconditioning regimens can enhance CAR activity in vivo by promoting T-cell expansion and depleting immunoinhibitory cells that counteract cellular immunity. These nonspecific regimens, however, can be exceedingly toxic and contribute to poor quality of life...
August 2016: Neurosurgery
Li Wang, Huanwen Wu, Lili Wang, Junliang Lu, Huanli Duan, Xuguang Liu, Zhiyong Liang
BACKGROUND: The validation of novel diagnostic, prognostic and predictive biomarkers in cancer is crucial for optimizing the choice and efficacy of personalized therapies. The aim of this study was to determine the epidermal growth factor receptor (EGFR), epidermal growth factor receptor variant III (EGFRvIII) and amphiregulin (AREG) protein expression levels and to evaluate the prognostic significance of EGFR, EGFRvIII and AREG in pancreatic ductal adenocarcinoma (PDAC). METHODS: The EGFR, EGFRvIII and AREG protein levels in PDAC (n = 92) were examined by using immunohistochemistry...
2016: Diagnostic Pathology
Jian-Wei Wei, Jing-Qiu Cui, Xuan Zhou, Chuan Fang, Yan-Li Tan, Lu-Yue Chen, Chao Yang, Ming Liu, Chun-Sheng Kang
Extensive heterogeneity is a defining hallmark of glioblastoma multiforme (GBM) at the cellular and molecular levels. EGFRvIII, the most common EGFR mutant, is expressed in 24-67% of cases and strongly indicates a poor survival prognosis. By co-expressing EGFRvIII and EGFRwt, we established an EGFRvIII/wt heterogenic model. Using this approach, we confirmed that a mixture of EGFRvIII and EGFRwt at a certain ratio could clearly enhance tumor growth in vitro and in vivo compared with EGFRwt cells, thereby indicating that EGFRvIII cells promote tumor growth...
September 28, 2016: Cancer Letters
Genaro R Villa, Paul S Mischel
No abstract text is available yet for this article.
May 26, 2016: Nature Neuroscience
James Keller, Anjaruwee S Nimnual, Mathew S Varghese, Kristen A VanHeyst, Michael J Hayman, Edward L Chan
UNLABELLED: EGFR is a popular therapeutic target for many cancers. EGFR inhibitors have been tested in children with refractory neuroblastoma. Interestingly, partial response or stable disease was observed in a few neuroblastoma patients. As EGFR mutations are biomarkers for response to anti-EGFR drugs, primary neuroblastoma tumors and cell lines were screened for mutations. A novel EGFR extracellular domain deletion mutant, EGFRΔ768, was discovered and the biologic and biochemical properties of this mutant were characterized and compared with wild-type and EGFRvIII receptors...
August 2016: Molecular Cancer Research: MCR
Loan Bui, Alissa Hendricks, Jamie Wright, Cheng-Jen Chuong, Digant Davé, Robert Bachoo, Young-Tae Kim
Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII), and genetically modified mouse astrocytes (wild type, p53-/-, p53-/- PTEN-/-, p53-/- Braf, and p53-/- PTEN-/- Braf)...
2016: Scientific Reports
Cezary Treda, Marta Popeda, Magdalena Ksiazkiewicz, Dawid P Grzela, Maciej P Walczak, Mateusz Banaszczyk, Joanna Peciak, Ewelina Stoczynska-Fidelus, Piotr Rieske
The Epidermal Growth Factor Receptor (EGFR) and its mutations contribute in various ways to tumorigenesis and biology of human cancers. They are associated with tumor proliferation, progression, drug resistance and the process of apoptosis. There are also reports that overexpression and activation of wild-type EGFR may lead to cell apoptosis. To study this phenomenon, we overexpressed in an AD293 cell line two most frequently observed forms of the EGFR receptor: wild-type and the constitutively active mutant-EGFR variant III (EGFRvIII)...
2016: PloS One
Sabrina Genßler, Michael C Burger, Congcong Zhang, Sarah Oelsner, Iris Mildenberger, Marlies Wagner, Joachim P Steinbach, Winfried S Wels
Epidermal growth factor receptor (EGFR) and its mutant form EGFRvIII are overexpressed in a large proportion of glioblastomas (GBM). Immunotherapy with an EGFRvIII-specific vaccine has shown efficacy against GBM in clinical studies. However, immune escape by antigen-loss variants and lack of control of EGFR wild-type positive clones limit the usefulness of this approach. Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells may represent an alternative immunotherapeutic strategy. For targeting to GBM, we generated variants of the clinically applicable human NK cell line NK-92 that express CARs carrying a composite CD28-CD3ζ domain for signaling, and scFv antibody fragments for cell binding either recognizing EGFR, EGFRvIII, or an epitope common to both antigens...
April 2016: Oncoimmunology
Arezu Jahani-Asl, Hang Yin, Vahab D Soleimani, Takrima Haque, H Artee Luchman, Natasha C Chang, Marie-Claude Sincennes, Sidharth V Puram, Andrew M Scott, Ian A J Lorimer, Theodore J Perkins, Keith L Ligon, Samuel Weiss, Michael A Rudnicki, Azad Bonni
EGFRvIII-STAT3 signaling is important in glioblastoma pathogenesis. Here, we identified the cytokine receptor OSMR as a direct target gene of the transcription factor STAT3 in mouse astrocytes and human brain tumor stem cells (BTSCs). We found that OSMR functioned as an essential co-receptor for EGFRvIII. OSMR formed a physical complex with EGFRvIII, and depletion of OSMR impaired EGFRvIII-STAT3 signaling. Conversely, pharmacological inhibition of EGFRvIII phosphorylation inhibited the EGFRvIII-OSMR interaction and activation of STAT3...
June 2016: Nature Neuroscience
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